Research

Treatment-resistant metastasis is the predominant cause of prostate cancer (PCa)-related death. My laboratory research programme explores how post-transcriptional mechanisms of gene regulation underlie both the metastatic and treatment-resistant PCa phenotypes.

A major focus in our group is the role of a ubiquitous genetic process, termed alternative pre-mRNA splicing, where coding (exons) and non-coding (introns) regions of a gene are shuffled to create structurally/functionally different protein isoforms.  Alternative splicing is controlled by trans-acting RNA-binding proteins (RBPs), which bind cis-elements within the nascent pre-mRNA.  RBPs also have key roles in other aspects of RNA processing and metabolism.

We are exploring the expression and localization of RBPs in primary tumours and their contribution to the differential regulation of the transcriptome and proteome during disease progression.  We are also exploring how RNA-based liquid biopsy biomarkers may improve the prediction of treatment outcomes for PCa patients.

Our clinical research utilises large population-based PCa patient datasets to explore patterns associated with different treatment outcomes.

Ultimately, we hope to identify clinical risk prediction models and biomarkers, as well as delineate novel therapeutic strategies for metastatic and treatment-resistant PCa.

Other Activities

• 2019 to date- Member: National Cancer Research Institute (NCRI) Teenage & Young Adults (TYA) and Germ Cell Tumours Clinical Studies Group (CSG) (Germ Cell Tumours Subgroup)
• 2019 to date- Member: NCRI Prostate Cancer CSG (Advanced Disease Subgroup)

Major Funding

• 2017-2021- The Urology Foundation/The John Black Charitable Foundation Project Grant, Androgen receptor splice variants in prostate cancer (Principal Investigator), £249,999
• 2013-2019- Royal College of Surgeons of England/Cancer Research UK- Clinician Scientist Fellowship in Surgery, Analysis of alternative splicing in prostate cancer metastasis regulated by the RNA-binding proteins Sam68 and hnRNP A2/B1 (Principal Investigator), >£800,000

Recent Publications

Non-invasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells. Xu L, Mao X, Grey A et al. J Urol (2019) (2) 101097JU000000000000
https://www.ncbi.nlm.nih.gov/pubmed/31389764

Pathological Findings and Magnetic Resonance Imaging Concordance at Salvage Radical Prostatectomy for Local Recurrence following Partial Ablation Using High Intensity Focused Ultrasound. Thompson JE, Sridhar AN, Tan WS et al. J Urol (2019) 201(1) 1134-1143
https://www.ncbi.nlm.nih.gov/pubmed/30730409

Androgen Receptor Burden and Poor Response to Abiraterone or Enzalutamide in TP53 Wild-Type Metastatic Castration-Resistant Prostate Cancer. De Laere B, Rajan P, Grönberg H et al. JAMA Oncol (2019) (1)
https://www.ncbi.nlm.nih.gov/pubmed/31046065

PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens. Heavey S, Costa H, Pye H et al. Prostate (2019) 79(2) 768-777
https://www.ncbi.nlm.nih.gov/pubmed/30807665

TP53 Outperforms Other Androgen Receptor Biomarkers to Predict Abiraterone or Enzalutamide Outcome in Metastatic Castration-Resistant Prostate Cancer. De Laere B, Oeyen S, Mayrhofer M et al. Clin Cancer Res (2019) 25(2) 1766-1773
https://www.ncbi.nlm.nih.gov/pubmed/30209161

Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis. Mayrhofer M, De Laere B, Whitington T et al. Genome Med (2018) 10(2) 85
https://www.ncbi.nlm.nih.gov/pubmed/30458854

Androgen-dependent alternative mRNA isoform expression in prostate cancer cells. Munkley J, Maia TM, Ibarluzea N et al. F1000Research (2018) 7(1) 1189-1189
https://www.ncbi.nlm.nih.gov/pubmed/30271587

A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. Foxler DE, Bridge KS, Foster JG et al. EMBO Mol Med (2018) (1)
https://www.ncbi.nlm.nih.gov/pubmed/29930174

Oncologic Outcomes After Robot-assisted Radical Prostatectomy: A Large European Single-centre Cohort with Median 10-Year Follow-up. Rajan P, Hagman A, Sooriakumaran P et al. Eur Urol Focus (2018) 4(2) 351-359
https://www.ncbi.nlm.nih.gov/pubmed/28753802

The practicing urologists’ guide to clinical research Lamb BW, Rajan P Journal of Clinical Urology (2018) (1)

Team

Postdoctoral Researchers
Dr Chinedu Anthony Anene, Dr John Foster

Research Technician
Ms Rebecca Arkell

Biography

Key qualifications